1. Field of Invention
This invention relates to a method for carrying out chemical reactions using as catalysts enzymes that are insolubilized or immobilized by bonding them to solid supporting materials, and in which a solution of the chemical reactants passes upward through a bed of such solid supporting material to which the enzymes of choice have been bound, such supporting material being in the form of particles of the proper size and density and the reactant solution flowing through the bed at such a rate that the bed of particles becomes expanded or fluidized and the advantages of fluidized bed operation are conferred upon the system and process thereby realized.
2. Description of Prior Art
Within the last decade the art of attaching enzymes to insoluble supporting materials has been developed and such solid-bound enzyme catalysts can now be applied to practical, commercial processes such as producing glucose from starch, hydrolyzing proteins and sugars, clarifying fruit juices and beer, carrying out reactions for producing antibiotic pharmaceutical reagents, treating human blood for promoting desired chemical reactions such as decomposition of urea, hydrolyzing the disaccharide lactose to its constituent monosaccharides glucose and galactose (especially the lactose in milk and in cheese whey), isomerizing the aldose D-glucose to the sweeter ketose D-fructose, selectively deacylating acyl L-amino acid within a D-L mixture of amino acids, clotting milk for cheese production with the enzyme rennin, and many other useful and potentially useful purposes. A major advantage of using enzymes in such insoluble form bound to a solid supporting material is that the catalytically active enzyme may be physically retained in the reaction vessel and contacted there with a continuously flowing liquid process stream. Before it was possible to bond enzymes to such insoluble supports, the enzymes would remain in the liquid process stream or could be separated therefrom only with difficulty with the result that the enzyme could be reused only with difficulty or not at all. Now that the art exists for bonding enzymes to insoluble supports, it becomes possible to use them in much the same way as ordinary heterogeneous catalysts on inert, insoluble supporting carriers that are well known in the chemical process industry. Such use now permits the continuous, convenient reuse of the same insolubilized enzyme catalyst for contacting a continuously flowing liquid reaction process stream thereby catalyzing a desired chemical reaction within said stream but without the necessity of separating the enzyme from the reaction products or the possible disadvantage of losing said enzyme entirely and not being able to re-use it.
However, some major problems have been encountered in the practical application of such insolubilized enzymes. They have usually been bonded to natural and synthetic high polymers and then used in fixed bed reactors; in such systems disadvantageously high pressure drop and plugging have been encountered and this behavior can be attributed to the small particle size and to the deformable, gel-like properties of the polymeric supporting material. More recent attempts to circumvent these kinds of problems have involved using inorganic supporting materials such as apatite and glass. While the latter materials are less deformable than the organic polymeric supports, columns packed with these materials still are susceptible to plugging and cause high pressure drop when small particle sizes are used in fixed, packed beds. When the particles are made sufficiently large to avoid such adverse plugging and pressure-drop behavior, their very size causes large mass transfer resistances both within the liquid film surrounding the support particles and within the support particles themselves if they are porous. Such mass transfer resistance can prevent the reactants from reaching the immobilized enzyme as fast as they can react and thereby can result in inefficient utilization of the enzyme bound to the solid support. To minimize mass transfer resistances, both within the solid supporting particles themselves and in the liquid film surrounding them, the particles should be as small as possible. However, as has already been stated, fixed packed beds of small particles are markedly susceptible to plugging and cause disadvantageously high pressure drops. Stirred-tank, slurry reactors are also susceptible to plugging and have the added disadvantages of back mixing, mechanical complexity and high shear rates.
Until the present invention there has been no simple way of utilizing insolubilized enzymes bound to solid supporting materials in a process that simultaneously provides relative freedom from plugging and from high pressure drops, reasonably high liquid flow rates in approximate plug flow and excellent mass transfer rates from process stream to the solid supporting particles and within the particles themselves. The present invention employs an expanded or fluidized bed of insoluble support particles to which enzyme is bound but the present invention differs from prior art in that expanded of fluidized bed processing has never before been applied to enzyme catalyzed reactions, in that the insoluble, support particles must have certain type of properties for good fluidization behavior in a fast flowing liquid stream, and in that said good fluidization properties are achieved by constructing the insolubilized-enzyme, catalyst particles in new and different ways. It should be emphasized that the solid, immobilized-enzyme particles of the present invention may be porous or non porous. Often porous particles, or non porous particles surrounded by porous outer layers, will be chosen in order to provide more surface area within pores where enzyme can be bound.